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Caveolae Link CaV3.2 Channels to BKCa-Mediated Feedback in Vascular Smooth Muscle.
Hashad, Ahmed M; Harraz, Osama F; Brett, Suzanne E; Romero, Monica; Kassmann, Mario; Puglisi, Jose L; Wilson, Sean M; Gollasch, Maik; Welsh, Donald G.
Afiliação
  • Hashad AM; From the Department of Physiology and Pharmacology, Hotchkiss Brain and Libin Cardiovascular Institutes, University of Calgary, Alberta, Canada (A.M.H., O.F.H., D.G.W.).
  • Harraz OF; From the Department of Physiology and Pharmacology, Hotchkiss Brain and Libin Cardiovascular Institutes, University of Calgary, Alberta, Canada (A.M.H., O.F.H., D.G.W.).
  • Brett SE; Department of Pharmacology, University of Vermont, Burlington (O.F.H.).
  • Romero M; Department of Physiology and Pharmacology, University of Western Ontario, London, Canada (S.E.B., D.G.W.).
  • Kassmann M; Advanced Imaging and Microscopy Core, Loma Linda University School of Medicine, CA (M.R., S.M.W.).
  • Puglisi JL; Experimental and Clinical Research Centre, Charité University Medicine, Berlin, Germany (M.K., M.G.).
  • Wilson SM; College of Medicine, California North State University, Sacramento (J.L.P.).
  • Gollasch M; Advanced Imaging and Microscopy Core, Loma Linda University School of Medicine, CA (M.R., S.M.W.).
  • Welsh DG; Experimental and Clinical Research Centre, Charité University Medicine, Berlin, Germany (M.K., M.G.).
Arterioscler Thromb Vasc Biol ; 38(10): 2371-2381, 2018 10.
Article em En | MEDLINE | ID: mdl-30354206
Objective- This study examined whether caveolae position CaV3.2 (T-type Ca2+ channel encoded by the α-3.2 subunit) sufficiently close to RyR (ryanodine receptors) for extracellular Ca2+ influx to trigger Ca2+ sparks and large-conductance Ca2+-activated K+ channel feedback. Approach and Results- Using smooth muscle cells from mouse mesenteric arteries, the proximity ligation assay confirmed that CaV3.2 reside within 40 nm of caveolin 1, a key caveolae protein. Methyl-ß-cyclodextrin, a cholesterol depleting agent that disrupts caveolae, suppressed CaV3.2 activity along with large-conductance Ca2+-activated K+-mediated spontaneous transient outward currents in cells from C57BL/6 but not CaV3.2-/- mice. Genetic deletion of caveolin 1, a perturbation that prevents caveolae formation, also impaired spontaneous transient outward current production but did so without impairing Ca2+ channel activity, including CaV3.2. These observations indicate a mistargeting of CaV3.2 in caveolin 1-/- mice, a view supported by a loss of Ni2+-sensitive Ca2+ spark generation and colocalization signal (CaV3.2-RyR) from the proximity ligation assay. Vasomotor and membrane potential measurements confirmed that cellular disruption of the CaV3.2-RyR axis functionally impaired the ability of large-conductance Ca2+-activated K+ to set tone in pressurized caveolin 1-/- arteries. Conclusions- Caveolae play a critical role in protein targeting and preserving the close structural relationship between CaV3.2 and RyR needed to drive negative feedback control in resistance arteries.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sinalização do Cálcio / Canais de Cálcio Tipo T / Cavéolas / Miócitos de Músculo Liso / Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta / Músculo Liso Vascular Limite: Animals Idioma: En Revista: Arterioscler Thromb Vasc Biol Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sinalização do Cálcio / Canais de Cálcio Tipo T / Cavéolas / Miócitos de Músculo Liso / Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta / Músculo Liso Vascular Limite: Animals Idioma: En Revista: Arterioscler Thromb Vasc Biol Ano de publicação: 2018 Tipo de documento: Article